DESCRIPTION (Adapted from the applicant's description) Recent studies have provided the first convincing evidence for a syndrome of sleep deprivation induced physiological changes, distinct from sleepiness. These include elevation of metabolic rate, alterations in thermoregulation, increased food intake and other symptoms. Whereas most of these changes appear to be neurological in origin and they ultimately lead to death, no neuropathological correlates of this syndrome have been detected. In pilot studies for this proposal, these investigators have used the De Olmos amino-cupric sliver technique to look for degenerative changes in the brains of sleep deprived rats. They found axonal and somatic degeneration in the hypothalamus and basal forebrain after 10 days of sleep deprivation. If confirmed in a larger group of animals, this would be the first clear evidence that sleep deprivation produces neuronal degeneration. Phylogenetic and ontogenetic evidence demonstrate that the major correlate of sleep time is body size, with larger animals having as little as 10% of the sleep time of smaller animals. They hypothesize that larger animals incur less free radical damage to their central nervous systems due to a more favorable balance between oxidative stress and the activity of antioxidative enzymes. These applicants will test the hypothesis that free radical damage occurs during sleep deprivation by using a newly developed assay that allows the immunological detection of carbonyl radicals, and by labeling for: 4-hydroxynonenal (HNE), an aldehyde product of lipid peroxidation; peroxynitrite a powerful oxidant; and heme oxygenase-1 (HO-1), an enzyme activated by oxidative stress. They will do these stains in conjunction with amino-cupric silver staining. They will attempt to reduce sleep deprivation induced damage by administration of the antioxidant PBN. They hypothesize that mammalian sleep enables elevated metabolic rate in waking, by providing an opportunity for repair of free radical damage in the central nervous system.